Plasmodium falciparum, an obligate intracellular parasite and causative agent
of malaria, exhibits an atypical metabolic organization of proteins which are diverged
extensively from their homologues in other organisms. This divergence makes
homology-based on structural and functional annotation of the proteins difficult. With
an emphasis on determinant aspects such as domain duplication, divergence and domain
splitting, we provide a comprehensive basis to understand the significance of sequence
divergence observed in metabolic proteins of P. falciparum. Such a pronounced
sequence divergence in proteins renders the homology-based annotation transfer nontrivial.
Additionally the unavailability of function annotation for about 40% of the
parasitic proteome poses a limitation to understand the physiological basis of metabolic
flexibility exhibited by the parasite to facilitate its multi-host survival. Thus, detection
and exploration of remotely related homologues with the help of highly sensitive
sequence search techniques become indispensable. Employment of a combination of
highly sensitive profile-based approaches has enabled enhanced structural and
functional characterization of metabolic proteins along with identification of proteins
potentially involved in metabolic pathways. An enriched function annotation of the
parasitic protein repertoire not only facilitates recognition of putative pathway proteins
but also paves way for prioritizing targets for chemotherapeutic interventions.
Keywords: Metabolic enzymes, metabolic pathways, Plasmodium falciparum,
protein evolution, remote homology detection.
